Characterization and chromosomal localization of human hair-specific keratin genes and comparative expression during the hair growth cycle.
During anagen, cell proliferation in the germinative matrix of the hair follicle gives rise to the fiber and inner root sheath. The hair fiber is constructed from structural proteins belonging to four multigene families: keratin intermediate filaments, high-sulfur matrix proteins, ultra high-sulfur matrix proteins, and high glycine-tyrosine proteins. Several hair-specific keratin intermediate filament proteins have been characterized, and all have relatively cysteine-rich N- and C-terminal domains, a specialization that allows extensive disulfide cross-linking to matrix proteins. We have cloned two complete type II hair-specific keratin genes (ghHb1 and ghHb6). Both genes have nine exons and eight introns spanning about 7 kb and lying about 10 kb apart. The structure of both genes is highly conserved in the regions that encode the central rod domain but differs considerably in the C-terminal coding and noncoding sequences, although some conservation of introns does exist. These genes have been localized to the type II keratin cluster on chromosome 12q13 by fluorescence in situ hybridization. They, and their type I partner ghHa1, are expressed in differentiating hair cortical cells during anagen. In cultured follicles, ghHa1 expression declined in cortical cells and was no longer visible after 6 d, whereas the basal epidermal keratin hK14 appeared in the regressing matrix. The transition from anagen to telogen is marked by downregulation of hair cortical specific keratins and the appearance of hK14 in the epithelial sac to which the telogen hair fiber is anchored. Further studies of the regulation of these genes will improve our understanding of the cyclical molecular changes that occur as the hair follicle grows, regresses, and rests.
Bowden
P E
PE
Department of Dermatology, UWCM, Cardiff, UK.
Hainey
S D
SD
Parker
G
G
Jones
D O
DO
Zimonjic
D
D
Popescu
N
N
Hodgins
M B
MB
D001483:Base Sequence; D002874:Chromosome Mapping; D003360:Cosmids / Q000235:genetics; D015870:Gene Expression / Q000502:physiology*; D006197:Hair / Q000254:growth & development* / Q000502:physiology*; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D007633:Keratins / Q000235:genetics*; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D012879:Skin Physiological Phenomena; D014158:Transcription, Genetic
D007633:Keratins